tbuckley/cabot-search huggingface dataset:
Phenotypes, Etiotypes, and Endotypes of Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Surya P. Bhatt, Alvar Agusti, Mona Bafadhel, Stephanie A. Christenson, Jessica Bon, Gavin C. Donaldson, Don D. Sin, Jadwiga A. Wedzicha, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Chronic obstructive pulmonary disease is a major health problem with a high prevalence, a rising incidence, and substantial morbidity and mortality. Its course is punctuated by acute episodes of increased respiratory symptoms, termed exacerbations of chronic obstructive pulmonary disease (ECOPD). ECOPD are important events in the natural history of the disease, as they are associated with lung function decline and prolonged negative effects on quality of life. The present-day therapy for ECOPD with short courses of antibiotics and steroids and escalation of bronchodilators has resulted in only modest improvements in outcomes. Recent data indicate that ECOPD are heterogeneous, raising the need to identify distinct etioendophenotypes, incorporating traits of the acute event and of patients who experience recurrent events, to develop novel and targeted therapies. These characterizations can provide a complete clinical picture, the severity of which will dictate acute pharmacological treatment, and may also indicate whether a change in maintenance therapy is needed to reduce the risk of future exacerbations. In this review we discuss the latest knowledge of ECOPD types on the basis of clinical presentation, etiology, natural history, frequency, severity, and biomarkers in an attempt to characterize these events.
A Geospatial Analysis of Disparities in Access to Oncofertility Services
Authors: Benjamin J. Peipert, Nivedita R. Potapragada, Paul M. Lantos, Benjamin S. Harris, Joyce Reinecke, Kara N. Goldman
Journal: JAMA Oncology (2023)

Fertility preservation (FP), including oocyte and embryo cryopreservation prior to gonadotoxic therapy, is an urgent and essential component of comprehensive cancer care. Geographic proximity to a center offering FP is a critical component of ensuring equitable access for people with cancer desiring future fertility.
Final 5-Year Follow-Up Results Evaluating Neoadjuvant Talimogene Laherparepvec Plus Surgery in Advanced Melanoma
Authors: Reinhard Dummer, David E. Gyorki, John R. Hyngstrom, Meng Ning, Tatiana Lawrence, Merrick I. Ross
Journal: JAMA Oncology (2023)

This randomized clinical trial presents the final 5-year follow-up results of neoadjuvant talimogene laherparepvec (T-VEC) plus surgery in patients with advanced melanoma.
The IGF2BP3–COPS7B Axis Facilitates mRNA Translation to Drive Colorectal Cancer Progression
Authors: Jing Tang, Shuoshuo Wang, Mingjiao Weng, Qingyu Guo, Lili Ren, Yan He, Zihan Cui, Mingqi Cong, Minglu Qin, Jia Yu, Rui Su, Xiaobo Li
Journal: Cancer Research (2023)

Many studies have provided valuable information about genomic and transcriptomic changes that occur in colorectal cancer. However, protein abundance cannot be reliably predicted by DNA alteration or mRNA expression, which can be partially attributed to posttranscriptional and/or translational regulation of gene expression. In this study, we identified increased translational efficiency (TE) as a hallmark of colorectal cancer by evaluating the transcriptomic and proteomic features of patients with colorectal cancer, along with comparative transcriptomic and ribosome-protected mRNA analysis in colon epithelial cells and colon cancer cells. COP9 signalosome subunit 7B (COPS7B) was among the key genes that consistently showed both significant TE increase and protein elevation without transcriptional alteration in colorectal cancer. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) enhanced the TE of COPS7B mRNA to promote colorectal cancer growth and metastasis. COPS7B was found to be a component of the ribo-interactome that interacted with ribosomes to facilitate ribosome biogenesis and mRNA translation initiation. Collectively, this study revealed the proteomic features of colorectal cancer and highlighted elevated mRNA translation as a hallmark of colorectal cancer. The identification of the IGF2BP3-COPS7B axis underlying the increased protein synthesis rate in colorectal cancer provided a promising therapeutic target to treat this aggressive disease.Increased expression of COPS7B mediated by IGF2BP3 elevates the translational efficiency of genes enriched in mRNA translation and ribosome biogenesis pathways, promoting protein synthesis and driving progression in colorectal cancer.
Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in <i>ERBB2</i>-Positive Metastatic Breast Cancer
Authors: Jens Huober, Patrik Weder, Karin Ribi, Beat Thürlimann, Jean-Christophe Thery, Qiyu Li, Laurence Vanlemmens, Séverine Guiu, Etienne Brain, Julien Grenier, Florence Dalenc, Christelle Levy, Aude-Marie Savoye, Andreas Müller, Véronique Membrez-Antonioli, Marie-Aline Gérard, Jérôme Lemonnier, Hanne Hawle, Daniel Dietrich, Epie Boven, Hervé Bonnefoi, Razvan Popescu, Alexander Schreiber, Clemens Caspar, Corinne Cescato- Wenger, Christoph Rochlitz, Rosaria Condorelli, Manuela Rabaglio-Poretti, Markus Borner, Catherine Mengis Bay, Lorenz M. Jost, Roger von Moos, Mathias Fehr, Alexandre Bodmer, Khallil Zaman, Bettina Seifer, Antonello Calderoni, Stefan Paul Aebi, Catrina Uhlmann Nussbaum, Salome Riniker, Barbara Bolliger, Christoph Ackermann, Konstantin Dedes, Céline Bihan, Olivier Capitain, Olivier Arsene, Hélène Simon, Mansour Rastkhah, Bruno Coudert, Mireille Mousseau, Laurance Venat- Bouvet, Régine Lamy, Véronique Brunel, Anthony Goncalves, Rémy Largillier, Dominique Spaeth, Jean- Michel Vannetzel, Jean- Marc Ferrero, Francesco Ricci, Cristina Rosca, Marc Baron, Mario Campone, Jean- Philippe Jacquin, Sebastian Serra, Francesco Del Piano, Dominique Dramais Marcel, Irma Ovign, Carolien Smorenburg, Inge Konings, Daniel Houtsma, Lonneke Kessels, Laurance van Warmerdam, Hiltje de Graaf, Judith Kroep, Mariette Agterof, Quirine van Rossum- Schornagel, Elise Van Leeuwen, Valérie Benavent, Christiane Pilop, Jerôme Lemonier, Anne Laure Martin, Christiane Ölschlegel, Marie- Aline Gérard, Michael Gnant, Sybille Loibl, Carlo Tondini
Journal: JAMA Oncology (2023)

In ERBB2 (formerly HER2)-positive metastatic breast cancer (MBC), combining trastuzumab and pertuzumab with taxane-based chemotherapy is the first line of standard care. Given that trastuzumab plus pertuzumab was proven effective in ERBB2-positive MBC, even without chemotherapy, whether the optimal first-line strategy could be trastuzumab plus pertuzumab alone instead of with chemotherapy is unresolved.
Relative effectiveness of bivalent Original/Omicron BA.4-5 mRNA vaccine in preventing severe COVID-19 in persons 60 years and above during SARS-CoV-2 Omicron XBB.1.5 and other XBB sublineages circulation, Italy, April to June 2023
Authors: Massimo Fabiani, Alberto Mateo-Urdiales, Chiara Sacco, Maria Cristina Rota, Emmanouil Alexandros Fotakis, Daniele Petrone, Martina Del Manso, Andrea Siddu, Paola Stefanelli, Antonino Bella, Flavia Riccardo, Giovanni Rezza, Anna Teresa Palamara, Silvio Brusaferro, Patrizio Pezzotti
Journal: Eurosurveillance (2023)

During predominant circulation of SARS-CoV-2 Omicron XBB.1.5 and other XBB sublineages (April-June 2023), we found that a second or third booster of Comirnaty bivalent Original/Omicron BA.4-5 mRNA vaccine, versus a first booster received at least 120 days earlier, was effective in preventing severe COVID-19 for more than 6 months post-administration in persons 60 years and above. In view of autumn 2023 vaccination campaigns, use of bivalent Original/Omicron BA.4-5 mRNA vaccines might be warranted until monovalent COVID-19 vaccines targeting Omicron XBB.1 sublineages become available.
A constitutional Voice in parliament would improve the health of Aboriginal Australians
Authors: Pat Anderson, Megan Davis, Toby Freeman, Fran Baum
Journal: BMJ (2023)

Australians are due to vote in a referendum on whether to amend the constitution to incorporate an Aboriginal and Torres Strait Islander Voice in parliament. Including this could improve the health, wellbeing, and autonomy of Aboriginal communities, write <b>Pat Anderson and colleagues</b>
Long term risk of death and readmission after hospital admission with covid-19 among older adults: retrospective cohort study
Authors: Andrew S Oseran, Yang Song, Jiaman Xu, Issa J Dahabreh, Rishi K Wadhera, James A de Lemos, Sandeep R Das, Tianyu Sun, Robert W Yeh, Dhruv S Kazi
Journal: BMJ (2023)

Abstract Objectives To characterize the long term risk of death and hospital readmission after an index admission with covid-19 among Medicare fee-for-service beneficiaries, and to compare these outcomes with historical control patients admitted to hospital with influenza. Design Retrospective cohort study. Setting United States. Participants 883 394 Medicare fee-for-service beneficiaries age ≥65 years discharged alive after an index hospital admission with covid-19 between 1 March 2020 and 31 August 2022, compared with 56 409 historical controls discharged alive after a hospital admission with influenza between 1 March 2018 and 31 August 2019. Weighting methods were used to account for differences in observed characteristics. Main outcome measures All cause death within 180 days of discharge. Secondary outcomes included first all cause readmission and a composite of death or readmission within 180 days. Results The covid-19 cohort compared with the influenza cohort was younger (77.9 v 78.9 years, standardized mean difference −0.12) and had a lower proportion of women (51.7% v 57.3%, −0.11). Both groups had a similar proportion of black beneficiaries (10.3% v 8.1%, 0.07) and beneficiaries with dual Medicaid-Medicare eligibility status (20.1% v 19.2%; 0.02). The covid-19 cohort had a lower comorbidity burden, including atrial fibrillation (24.3% v 29.5%, −0.12), heart failure (43.4% v 49.9%, −0.13), and chronic obstructive pulmonary disease (39.2% v 52.9%, −0.27). After weighting, the covid-19 cohort had a higher risk (ie, cumulative incidence) of all cause death at 30 days (10.9% v 3.9%; standardized risk difference 7.0%, 95% confidence interval 6.8% to 7.2%), 90 days (15.5% v 7.1%; 8.4%, 8.2% to 8.7%), and 180 days (19.1% v 10.5%; 8.6%, 8.3% to 8.9%) compared with the influenza cohort. The covid-19 cohort also experienced a higher risk of hospital readmission at 30 days (16.0% v 11.2%; 4.9%, 4.6% to 5.1%) and 90 days (24.1% v 21.3%; 2.8%, 2.5% to 3.2%) but a similar risk at 180 days (30.6% v 30.6%;–0.1%, −0.5% to 0.3%). Over the study period, the 30 day risk of death for patients discharged after a covid-19 admission decreased from 17.9% to 7.2%. Conclusions Medicare beneficiaries who were discharged alive after a covid-19 hospital admission had a higher post-discharge risk of death compared with historical influenza controls; this difference, however, was concentrated in the early post-discharge period. The risk of death for patients discharged after a covid-19 related hospital admission substantially declined over the course of the pandemic.
Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks
Authors: Nathan Mullen, James Curneen, Padraig T Donlon, Punit Prakash, Irina Bancos, Mark Gurnell, Michael C Dennedy
Journal: Endocrine Reviews (2023)

Abstract Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared with blood pressure–matched cases of primary hypertension. Current limitations in patient care stem from delayed recognition of the condition, limited access to key diagnostic procedures, and lack of a definitive therapy option for nonsurgical candidates. However, several recent advances have the potential to address these barriers to optimal care. From a diagnostic perspective, machine-learning algorithms have shown promise in the prediction of PA subtypes, while the development of noninvasive alternatives to adrenal vein sampling (including molecular positron emission tomography imaging) has made accurate localization of functioning adrenal nodules possible. In parallel, more selective approaches to targeting the causative aldosterone-producing adrenal adenoma/nodule (APA/APN) have emerged with the advent of partial adrenalectomy or precision ablation. Additionally, the development of novel pharmacological agents may help to mitigate off-target effects of aldosterone and improve clinical efficacy and outcomes. Here, we consider how each of these innovations might change our approach to the patient with PA, to allow more tailored investigation and treatment plans, with corresponding improvement in clinical outcomes and resource utilization, for this highly prevalent disorder.
Immunotherapy in the Treatment of Localized Genitourinary Cancers
Authors: Andrea Necchi, Bishoy M. Faltas, Susan F. Slovin, Joshua J. Meeks, Sumanta K. Pal, Lawrence H. Schwartz, Richard S. P. Huang, Roger Li, Brandon Manley, Jad Chahoud, Jeffrey S. Ross, Philippe E. Spiess
Journal: JAMA Oncology (2023)

A true revolution in the management of advanced genitourinary cancers has occurred with the discovery and adoption of immunotherapy (IO). The therapeutic benefits of IO were recently observed not to be solely confined to patients with disseminated disease but also in select patients with localized and locally advanced genitourinary neoplasms.
The importance of the gut microbiome in the pathogenesis and transmission of SARS-CoV-2
Authors: Carlo Brogna, Valentina Viduto, Mark Fabrowski, Simone Cristoni, Giuliano Marino, Luigi Montano, Marina Piscopo
Journal: Gut Microbes (2023)

Zhou et al. study nicely traces a significant topic in COVID-19 infection: the persistence of the virus within the intestinal tract. Many pathological mechanisms have been noted in the current literature about the mode of infection and propagation of SARS-CoV-2 in the human body. Nevertheless, there are still many concerns about this: only some things seem well understood. We present a different point of view by illustrating the importance of the gut microbiome in the pathogenesis of COVID-19 disorders.
Revisiting the personal protective equipment components of transmission-based precautions for the prevention of COVID-19 and other respiratory virus infections in healthcare
Authors: Diamantis Plachouras, Oliver Kacelnik, Jesús Rodríguez-Baño, Gabriel Birgand, Michael A Borg, Brian Kristensen, Jan Kubele, Outi Lyytikäinen, Elisabeth Presterl, Jacqui Reilly, Andreas Voss, Walter Zingg, Carl Suetens, Dominique L Monnet
Journal: Eurosurveillance (2023)

The COVID-19 pandemic highlighted some potential limitations of transmission-based precautions. The distinction between transmission through large droplets vs aerosols, which have been fundamental concepts guiding infection control measures, has been questioned, leading to considerable variation in expert recommendations on transmission-based precautions for COVID-19. Furthermore, the application of elements of contact precautions, such as the use of gloves and gowns, is based on low-quality and inconclusive evidence and may have unintended consequences, such as increased incidence of healthcare-associated infections and spread of multidrug-resistant organisms. These observations indicate a need for high-quality studies to address the knowledge gaps and a need to revisit the theoretical background regarding various modes of transmission and the definitions of terms related to transmission. Further, we should examine the implications these definitions have on the following components of transmission-based precautions: (i) respiratory protection, (ii) use of gloves and gowns for the prevention of respiratory virus infections, (iii) aerosol-generating procedures and (iv) universal masking in healthcare settings as a control measure especially during seasonal epidemics. Such a review would ensure that transmission-based precautions are consistent and rationally based on available evidence, which would facilitate decision-making, guidance development and training, as well as their application in practice.
Liposomal co-delivery of toll-like receptors 3 and 7 agonists induce a hot triple-negative breast cancer immune environment
Authors: Bao Loc Nguyen, Cao Dai Phung, Duc-Vinh Pham, Ngoc Duy Le, Jee-Heon Jeong, Jeonghwan Kim, Ju-Hyun Kim, Jae-Hoon Chang, Sung Giu Jin, Han-Gon Choi, Sae Kwang Ku, Jong Oh Kim
Journal: Journal of Controlled Release (2023)
Rates of Induction of Labor at 39 Weeks and Cesarean Delivery Following Publication of the ARRIVE Trial
Authors: Rachel Wood, Taylor S. Freret, Mark Clapp, Sarah Little
Journal: JAMA Network Open (2023)

This cross-sectional study analyzes the rates of induction and cesarean delivery before and after the publication of A Randomized Trial of Induction vs Expectant Management (ARRIVE).
HDACi-dependent Microenvironmental Normalization Overcomes Tumor Burden–induced T-cell Exhaustion
Authors: Andrew Nguyen, Dominique Brown, Ramya Krishnan, Donald Bastin, Li Deng, Lan Chen, Omar Salem, Scott R. Walsh, Jonathan L. Bramson, Yonghong Wan
Journal: Clinical Cancer Research (2023)

Abstract Purpose: T-cell exhaustion limits immunotherapy for the treatment of solid tumors. Although immune checkpoint blockade and adoptive T-cell therapy (ACT) can mediate tumor regression, their potency is often determined by tumor burden. Here, we identified tumor burden–related pathway changes that are conducive to T-cell exhaustion. We then determined whether microenvironmental reprogramming via epigenetic modulation could reverse T-cell exhaustion and improve immunotherapeutic responsiveness. Experimental Design: We developed a murine syngeneic tumor model wherein an increased burden ablated therapeutic responsiveness to ACT, which corresponded with systemic induction of T-cell exhaustion. Transcriptome analysis of these large tumors allowed us to characterize changes to immunosuppressive pathway expression during class I histone deacetylase inhibitor MS-275 treatment. We then measured the therapeutic impact of MS-275 during ACT and assessed T-cell exhaustion by transcriptome/phenotypic analysis. Results: ACT durably regressed small tumors but failed to control large tumors, which were associated with systemic T-cell exhaustion and ablation of T-cell responses. Large tumors were defined by an immunosuppressive pathway signature. MS-275 reversed this pathway signature and promoted durable regression of large tumors during ACT. Prototypical exhaustion marker Tim-3 was selectively upregulated in transferred T cells despite displaying a reduced exhaustion signature. Instead, we observed enhanced activation-dependent signaling correlating with enrichment of the IL2–STAT5 signaling axis. Activated CD8+ T-cell responses were predominantly skewed toward terminal effector cell–like CD44+ Tim-3hi TCF1− CD127− KLRG1+ differentiation. Conclusions: Tumor burden–induced pathway changes can be reversed through epigenetic reprogramming, enabling the conversion from T-cell exhaustion to effector lineage differentiation.
Stigma is stopping an evidence based response to drug overdose deaths in the UK
Authors: Andy Guise, Magdalena Harris, Martin McCusker, Ryan McNeil, Dan Werb
Journal: BMJ (2023)

Stigma is stopping an evidence based response to drug overdose deaths in the UKAndy Guise and colleagues argue that UK government opposition to drug consumption rooms is underpinned by, and reproduces stigma towards, drug use and people who use drugs
Five-Year Trajectories of Prescription Opioid Use
Authors: Natasa Gisev, Luke Buizen, Ria E. Hopkins, Andrea L. Schaffer, Benjamin Daniels, Chrianna Bharat, Timothy Dobbins, Sarah Larney, Fiona Blyth, David C. Currow, Andrew Wilson, Sallie-Anne Pearson, Louisa Degenhardt
Journal: JAMA Network Open (2023)

Importance There are known risks of using opioids for extended periods. However, less is known about the long-term trajectories of opioid use following initiation. Objective To identify 5-year trajectories of prescription opioid use, and to examine the characteristics of each trajectory group. Design, Setting, and Participants This population-based cohort study conducted in New South Wales, Australia, linked national pharmaceutical claims data to 10 national and state data sets to determine sociodemographic characteristics, clinical characteristics, drug use, and health services use. The cohort included adult residents (aged ≥18 years) of New South Wales who initiated a prescription opioid between July 1, 2003, and December 31, 2018. Statistical analyses were conducted from February to September 2022. Exposure Dispensing of a prescription opioid, with no evidence of opioid dispensing in the preceding 365 days, identified from pharmaceutical claims data. Main Outcomes and Measures The main outcome was the trajectories of monthly opioid use over 60 months from opioid initiation. Group-based trajectory modeling was used to classify these trajectories. Linked health care data sets were used to examine characteristics of individuals in different trajectory groups. Results Among 3 474 490 individuals who initiated a prescription opioid (1 831 230 females [52.7%]; mean [SD] age, 49.7 [19.3] years), 5 trajectories of long-term opioid use were identified: very low use (75.4%), low use (16.6%), moderate decreasing to low use (2.6%), low increasing to moderate use (2.6%), and sustained use (2.8%). Compared with individuals in the very low use trajectory group, those in the sustained use trajectory group were older (age ≥65 years: 22.0% vs 58.4%); had more comorbidities, including cancer (4.1% vs 22.2%); had increased health services contact, including hospital admissions (36.9% vs 51.6%); had higher use of psychotropic (16.4% vs 42.4%) and other analgesic drugs (22.9% vs 47.3%) prior to opioid initiation, and were initiated on stronger opioids (20.0% vs 50.2%). Conclusions and relevance Results of this cohort study suggest that most individuals commencing treatment with prescription opioids had relatively low and time-limited exposure to opioids over a 5-year period. The small proportion of individuals with sustained or increasing use was older with more comorbidities and use of psychotropic and other analgesic drugs, likely reflecting a higher prevalence of pain and treatment needs in these individuals.
<scp>Genome‐Wide</scp> Association Study Identifies the First Germline Genetic <scp>Variant Associated</scp> With <scp>Erdheim‐Chester</scp> Disease
Authors: Javier Martínez‐López, Ana Márquez, Francesco Pegoraro, Lourdes Ortiz‐Fernández, Marialbert Acosta‐Herrera, Martin Kerick, Elena Gelain, Eli L. Diamond, Benjamin H. Durham, Omar Abdel‐Wahab, Ronald S. Go, Matthew J. Koster, Lorenzo Dagna, Corrado Campochiaro, Matthew Collin, Paul Milne, Juvianee I. Estrada‐Veras, Kevin O'Brien, Matthias Papo, Fleur Cohen‐Aubar, Zahir Amoura, Julien Haroche, Javier Martín, Augusto Vaglio
Journal: Arthritis & Rheumatology (2023)

Objective Erdheim‐Chester disease (ECD) is rare histiocytosis with a wide range of clinical manifestations. Somatic mutations are key to the pathogenesis of the disease; however, the relationship between germline genetic variants and ECD has not been examined so far. The present study aims to explore the inherited genetic component of ECD by performing the first genome‐wide association study. Methods After quality controls, a cohort of 255 patients with ECD and 7,471 healthy donors was included in this study. Afterward, a logistic regression followed by in silico functional annotation was performed. Results A signal at the 18q12.3 genomic region was identified as a new susceptibility locus for ECD ( P = 2.75 × 10 −11 ; Odds Ratio = 2.09). This association was annotated to the SETBP1 gene, which is involved in clonal haematopoiesis. Functional annotation of this region and of the identified suggestive signals revealed additional genes that could be potentially involved in the pathogenesis of the disease. Conclusion Overall, this work demonstrates that germline genetic variants can impact on the development of ECD and suggests new pathways with a potential pathogenic role. image